Primary liver cancer, composed of two major histologic types, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the sixth most frequently occurring cancer in the world and the second most common cause of cancer mortality. While over 80% of liver cancers occur in Asia and sub-Saharan Africa, incidence has been increasing in low-rate areas, such as the U.S. and Europe, for several decades. Our research has been focusing on identifying factors associated with this increase in incidence. While excessive alcohol consumption and hepatitis C virus infection are major risk factors, our research has found that the risk attributable to diabetes and obesity is greater than the risk attributable to other factors. To follow-up on these findings, we are examining the contributions of these factors in 2 U.S. based research studies. We are also examining whether medications such as anti-diabetic drugs, non-steroidal anti-inflammatory drugs and statins affect the risk of liver cancer in developed countries.